FUNCTIONAL BRAIN MAPPING OF COCAINE ACTION

可卡因作用的大脑功能图谱

• 批准号: 6175697
• 负责人: BRUCE R ROSEN
• 金额: $ 113.09万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6175697
• 关键词: bioimaging /biomedical imaging; brain imaging /visualization /scanning; brain mapping; cocaine; drug addiction; functional magnetic resonance imaging

A major unmet goal of drug abuse research is to understand the neural substrates of reinforcement of drugs of abuse in humans and the role that these mechanisms may play in initiating and sustaining drug dependence. This proposal for a Program Project is a renewal of our currently funded PO1 from the National Institute on Drug Abuse, "fMRI of Cocaine Action". The overall goal of this program continues to be the utilization and refinement of state of the art techniques to produce interpretable brain maps, functional anatomy of human subjective states that occur in response to c0caine, with particular emphasis during the funding cycle on the braid reward circuitry mediating cocaine response in humans, using functional magnetic resonance imaging (fMRI) as the principal tool. To effectively perform the experiments to test these hypotheses, three Projects and three Cores. As in our current funding cycle, Project 1 is an fMRI study of regional brain activation by cocaine in cocaine-dependent human subjects. The objective of Project 1 is to investigate of brain reward circuitry in mediating the cocaine response in humans, and to distinguish euphoria-like brain activation from craving-like brain activation. Project 2 has evolved to begin the important work of developing rodent models to more completely understand pharmacologically mediated MRI signal changes observed after administration of dopamine ligands. The studies proposed in Project 2 are of fundamental importance for understanding and interpreting functional imaging data following cocaine administration in animals and humans. Project 3 utilizes rodent models, including both drug-naive and cocaine- dependent rats and, new to this funding cycle, knockout mice, to address specific pharmacological and drug dependence issues which cannot be readily addressed in humans. We anticipate that results from these experiments, will identify the role of particular neurotransmitter mechanisms (namely, dopaminergic and serotonergic) that underlie the pattern of cocaine-induced brain activation. The hypothesis driven experiments using state of the art functional imaging techniques that we proposed in Project 1, in concert with experiments proposed in Project 2 focused on identifying mechanisms coupling psychostimulant administration to cerebrovascular response, are designed to provide a deeper understanding of the mechanism of cocaine action. The Program Project mechanism is ideal for a multi-disciplinary project with these goals in mind. We anticipate that the experiments in rodents will advance our understanding of acute and chronic effects of cocaine on brain function, facilitating interpretation of data from Project 1, thereby providing a crucial effects of cocaine on brain function, facilitating interpretation of data from Project, thereby providing a crucial link in understanding the fMRI correlates and neurobiology consequences of cocaine addiction in humans.

药物滥用研究的一个主要未实现的目标是了解人类药物滥用强化的神经基质以及这些机制在启动和维持药物依赖中可能发挥的作用。本项目提案是对国家药物滥用研究所目前资助的PO1项目“可卡因作用的功能磁共振成像”的更新。该项目的总体目标仍然是利用和改进最先进的技术来制作可解释的大脑图谱，人类对可卡因反应的主观状态的功能解剖，在资助周期中特别强调编织奖励回路介导人类可卡因反应，使用功能磁共振成像（fMRI）作为主要工具。为了有效地进行实验来验证这些假设，三个项目和三个核心。就像我们目前的资金周期一样，项目1是一项功能磁共振成像研究，研究可卡因对可卡因依赖者大脑区域的激活。项目1的目的是研究人类大脑奖赏回路在介导可卡因反应中的作用，并区分欣快样大脑激活和渴望样大脑激活。项目2已经发展为开始开发啮齿动物模型的重要工作，以更全面地了解多巴胺配体给药后观察到的药理学介导的MRI信号变化。项目2中提出的研究对于理解和解释动物和人类服用可卡因后的功能成像数据具有重要意义。项目3利用啮齿类动物模型，包括未接触药物和可卡因依赖的大鼠，以及这个融资周期的新成员，敲除小鼠，来解决在人类身上无法轻易解决的特定药理学和药物依赖问题。我们预计这些实验的结果将确定特定神经递质机制（即多巴胺能和血清素能）的作用，这些机制是可卡因诱导的大脑激活模式的基础。我们在项目1中提出的假设驱动实验使用了最先进的功能成像技术，与项目2中提出的实验一致，重点是确定精神兴奋剂给药与脑血管反应的耦合机制，旨在更深入地了解可卡因作用的机制。程序项目机制对于具有这些目标的多学科项目是理想的。我们期望在啮齿类动物中进行的实验将促进我们对可卡因对脑功能的急性和慢性影响的理解，促进对项目1数据的解释，从而提供可卡因对脑功能的关键影响，促进对项目数据的解释，从而为理解人类可卡因成瘾的fMRI相关性和神经生物学后果提供关键环节。